Visual Abstract

Diabetic kidney disease (DKD) is the leading cause of end stage kidney disease (ESKD). Higher rates of death and ESKD are seen in YO vs. AO T2D; however, no studies have evaluated differences in structural lesions from kidney biopsies in YO and AO T2D. 161 Pima Indians with T2D underwent kidney biopsies. Quantitative morphometry was performed and participants were stratified as YO (<25 yrs) or AO T2D (≥25 yrs) based on age of onset ascertained by serial testing. Associations between morphometric parameters and age of onset (dichotomized as YO/AO, or age at onset as a continuous variable) were tested by linear models. Analyses included 52 participants with YO and 109 with AO T2D with mean±SD age of onset 19.8±4.2 and 34.4±7.5 yrs, glomerular filtration rate 154.8±55.9 and 138.0±51.8 ml/min (p=0.06), albumin:creatinine ratio median (25th, 75th %ile) 57.6 (17.1, 507.8) and 26.6 (13.9, 81.0) (p=0.023). Those with YO T2D had higher glomerular basement membrane (GBM) width (576 [540, 613] nm vs. 505 [482, 528] nm, p=0.002) and mesangial fractional volume (VvMes) (0.32 [0.30, 0.35] vs. 0.27 [0.25, 0.29], p=0.001). Percentage glomerular sclerosis, glomerular volume, VvMes, and GBM width were negatively related to age of onset (Table). Younger age of T2D onset strongly associated with more severe structural lesions. Future studies are needed to elucidate pathways underlying these associations.

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Disclosure

H. C. Looker: None. C. Severn: None. T. B. Vigers: None. L. Pyle: None. P. Saulnier: None. B. Najafian: Consultant; Self; 4DMT, Sangamo Therapeutics, Sanofi Genzyme, Research Support; Self; Amicus. M. Mauer: Consultant; Self; Freeline Therapeutics, Research Support; Self; Amicus, Sanofi Genzyme. R. G. Nelson: None. P. Bjornstad: Advisory Panel; Self; XORTX Therapeutics Inc., Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly Diabetes, Novo Nordisk, Research Support; Self; Horizon Therapeutics plc.

Funding

American Diabetes Association (1-08-CR-42 to R.G.N.); National Institute of Diabetes and Digestive and Kidney Diseases (DK116720, DK114886); JDRF (2-SRA-2019-845-S-B); Boettcher Foundation

© 2021 by the American Diabetes Association
2021
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